ReviewTransfusion-related immunomodulation (TRIM): An update
Section snippets
History and definition of TRIM
Over 30 years ago, it was reported that pre-transplant ABTs could improve renal-allograft survival in patients who had undergone renal transplantation.9 This beneficial immunosuppressive effect of ABT has been confirmed by animal data, observational clinical studies, and clinical experience worldwide, although it has not been proven in randomized controlled trials (RCTs). Before the advent of the AIDS pandemic, it had become standard policy in many renal units to deliberately expose patients on
Possible mechanisms and mediators of TRIM effects
Although the mechanisms of TRIM have been debated extensively, the exact mechanism(s) of this phenomenon has yet to be elucidated. A number of putative mechanisms have been postulated and are summarized in Table 1.7, 8 The three major mechanisms accounting for much of the experimental data include: clonal deletion, induction of anergy, and immune suppression. Conceptually, clonal deletion refers to the inactivation and removal of alloreactive lymphocytes that would, for example, cause the
Inferences on TRIM mediators permitted by RCTS investigating adverse TRIM effects
Twenty-two RCTs20, 21, 22, 50, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 have investigated the adverse TRIM effects potentially attributable to WBC-containing ABT. Table 2 categorizes these RCTs based on the type of RBC product transfused to patients in the arm receiving RBC products depleted of allogeneic WBCs and/or allogeneic plasma. Patients assigned randomly to this arm received (pre- or post-storage-filtered) WBC-reduced allogeneic RBCs or whole blood, or
Preclinical and clinical studies of the “pro-inflammatory” effect of ABT
The Canadian before-and-after study of premature infants,97 did not observe a difference in mortality or in the risk of bacteremia between the two study periods (before or after implementation of universal WBC reduction). Instead, the implementation of WBC reduction coincided with a reduction in several secondary morbidity outcomes from several organ systems (i.e., bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis)-an observation that would be consistent with a
Conclusions
The totality of the evidence from RCTs does not demonstrate a TRIM effect manifest across all clinical settings and transfused RBC products. Instead, WBC-containing ABT is associated with an increased risk of short-term (up to 3-month post transfusion) mortality from all causes combined specifically in cardiac surgery. The additional deleterious TRIM effect detected by the latest meta-analysis95 (i.e., the effect on postoperative infection prevented by poststorage filtration) contradicts
References (132)
Immunological aspects of blood transfusions
Transpl Immunol
(2002)Red blood cells for cancer patients
Lancet
(1981)- et al.
Controlled trial of treatment of recurrent spontaneous abortion by immunization with paternal cells
Lancet
(1985) - et al.
Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction?
Blood
(2001) - et al.
Evolving concepts in the pathogenesis of postinjury multiple-organ failure
Surg Clin North Am
(1995) Possible mechanisms of allogeneic blood transfusion-associated postoperative infection
Transf Med Rev
(2002)- et al.
The before/after study design in transfusion medicine: Methodologic considerations
Transf Med Rev
(2002) Apoptosis, TGF-beta, and transfusion-related immunosuppression: Biologic versus clinical effects
Transfusion Apheresis Sci
(2003)Induction of humoral immune tolerance to major histocompatibility complex antigens by transfusions of UV-B irradiated leukocytes
Blood
(1996)- et al.
Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells
Blood
(1993)
TGF-β in infections and infectious disease
Microbes and Infection
Transfusion-associated microchimerism: a new complication of blood transfusions in severely ill patients
Semin Hematol
Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients
Blood
Survival of transfused donor white blood cells in HIV-infected recipients
Blood
Human eosinophil cationic proteins (ECP and EPX) and their suppressive effects on lymphocyte proliferation
Immunobiology
Soluble HLA Class I, HLA Class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusion
Blood
Growth enhancement of established tumors by allogeneic blood transfusion in experimental animals and its amelioration by leukodepletion: the importance of timing of the leukodepletion
Blood
Transforming growth factor-beta-1 in supernatants from stored red blood cells inhibits neutrophil locomotion
Blood
Peptide-mediated immunosuppression
Curr Opin Immunol
Induction of tolerance by intrathymic inoculation of alloantigen
Curr Opin Immunol
Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery
Lancet
Randomized controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer
Lancet
Randomized comparison of leucocyte-depleted versus buffy-coat-poor blood transfusion and complications after colorectal surgery
Lancet
Autologous blood transfusion: The benefits for the patient undergoing abdominal aortic aneurysm repair
J Vasc Nurs
Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma
Burns
Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery
Am J Surg
Autologous blood transfusion in total knee replacement surgery
Br J Anaesth
Autologous transfusion and other approaches to reduce allogeneic blood exposure
Transfusion-related acute lung injury
Blood
Blood transfusion induced changes in cell-mediated lympholysis: to immunize or not to immunize
J Immunol
Immunomodulation by blood transfusions
Vox Sang
New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs
Ann Surg
T-cell costimulatory pathways in allograft rejection and tolerance
Immunol Rev
Costimulatory signals necessary for induction of T cell proliferation
Transplantation
Mechanisms of transfusion-induced immunosuppression
Transfusion
Mechanisms of transfusion-associated immunosuppression
Curr Opin Hematol
Effect of blood transfusions on subsequent kidney transplants
Transplant Proc
Multiple blood transfusions reduce the recurrence rate of Crohn’s disease
Dis Colon Rectum
Biologic effects of leukocytes present in transfused cellular blood products
Blood
Effects of transfusion on immune function: cancer recurrence and infection
Arch Pathol Lab Med
Blood transfusions and postoperative septic complications
Transfusion
Deleterious clinical effects of transfusion immunomodulation: proven beyond reasonable doubt
Transfusion
Deleterious clinical effects of transfusion immunomodulation: proved beyond reasonable doubt
Transfusion
Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: A randomized clinical trial
Circulation
Double-blind, randomized controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in cardiac valve surgery
Circulation
Prestorage leukoreduction of red cells in elective cardiac surgery: Results of a double-blind randomized controlled trial
Blood
Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock
Surgery
Multiple-organ failure: Inflammatory priming and activation sequences promote autologous tissue injury
J Trauma
Postinjury neutrophil priming and activation states: Therapeutic challenges
Shock
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